On 29 June, at the 12th Congress of the European Academy of Neurology (EAN) 2026, as part of a late-breaking e-poster session, Phase II program outcomes were presented for Lundbeck’s anti-pituitary adenylate cyclase-activating polypeptide (PACAP) monoclonal antibody (mAb) bocunebart as a preventive treatment for migraine. The Phase II program for bocunebart consisted of a Phase IIa proof-of-concept trial (HOPE: NCT05133323) and a Phase IIb dose finding and route of administration (subcutaneous [SC] and intravenous [IV]) trial (PROCEED: NCT06323928).
The primary endpoint of PROCEED was met with bocunebart (IV dose A) treatment resulting in a statistically significant reduction in monthly migraine days (MMD) from baseline compared with placebo over Weeks 1–12. Further, there were no new safety concerns seen in the PROCEED trial with bocunebart generally well tolerated across both Phase II trials.
The rest of the poster considered the efficacy of bocunebart in a pooled post-hoc analysis of all doses and all trial parts across both the HOPE and PROCEED trials in a total of 1,110 patients with chronic migraine. The post-hoc analysis demonstrated that patients treated with bocunebart achieved a greater reduction from baseline in MMDs and monthly headache days compared with placebo at Week 12. The bocunebart treatment group also saw a greater reduction in MMDs with acute medication use compared with the placebo group. Additionally, bocunebart treatment had a positive impact on function and quality of life for patients. Using the Migraine-Specific Quality of Life Questionnaire, patients who received bocunebart reported greater improvements in daily functioning and activity limitation (role function-restrictive and role function-preventive) and improvements in emotional function compared with placebo.
The current preventive landscape in migraine is highly competitive, especially since the launch of the calcitonin gene related peptide (CGRP)-targeting therapies, first with the mAbs and then the gepants. By targeting the pathophysiology of migraines, these therapies transformed the preventive market by providing treatment options with both more efficacy and better tolerability than the old oral preventives, such as beta blockers, antidepressants, and anti-epileptics, which were not specifically developed for or originally approved for migraine but showed some efficacy in clinical trials. However, despite the successes of anti-CGRP therapies, key opinion leaders (KOLs) previously interviewed by GlobalData noted that not everyone responds to them, and so an unmet need remains for treatment refractory patients.
Like CGRP, the neuropeptide PACAP is believed to be a key signalling molecule in the pathophysiology of migraine. Notably, PACAP represents the first genuinely novel mechanism of action to reach late-stage migraine development since CGRP was identified, positioning bocunebart as a potential first-in-class therapy in an otherwise thin pipeline of novel late-stage candidates. Unsurprisingly, KOLs consistently highlighted bocunebart as the most promising late-stage migraine pipeline drug, anticipating its success particularly in patients who don’t respond to the CGRP-targeting drugs. Indeed, key inclusion criteria from the Phase II trials was that patients had failed between one and four migraine prevention medications in the previous 10 years, indicating that Lundbeck is going after that patient population. This would remove some of the direct competition bocunebart would face against the highly successful CGRP therapies and give bocunebart a unique position in the migraine preventive market, albeit later in the treatment algorithm.
However, in 2024, the American Headache Society published a statement recommending that the CGRP-targeting drugs be used as first-line preventive therapies. This means that patients who are refractory to those therapies will be identified sooner, allowing for potential earlier use of bocunebart, increasing the potential opportunity for the drug in the preventive migraine space.
